Existing structures for blood flow, such as hollow fibers, tubing, and machined structures are typically produced using conventional macroscale chemical and mechanical processing techniques. Microfluidic devices are typically fabricated using conventional lithographic or etching techniques combined with replica molding. The methods for generating these structures that attempt to mimic vascular networks typically suffer from difficulties in reproducing, on the microscale, the specific and vitally important features of blood vessels. Methods using hollow fibers or other tubular structures and machined or stereolithographically formed elements for therapeutic devices, such as renal dialysis cartridges, liver assist devices, and pulmonary support devices, are typically limited in terms of the minimum diameter achievable. In addition, vessel bifurcations in tube and fiber-based constructs typically contain sharp angles due to limitations in the assembly processes. These limitations also introduce sudden changes in diameter at vessel diameter expansions and contractions. The sharp and sudden non-physiologic features lead to disturbed flow and poor control over key parameters, such as wall shear stress, leading to increased levels of inflammation and clotting and difficulties in seeding cells along the walls of the channels.
Microfluidic devices have addressed some of the shortfalls associated with fiber, tubing, and machining or solid freeform techniques. Principally, microfluidics has enabled a dramatic reduction in minimum feature size and simplification of the assembly processes. However, existing microfluidic fabrication techniques typically do not enable smooth transitions at bifurcations or vessel diameter changes, because the processes used to build the microfluidic master molds often result in rectangular geometries and do not enable tapered transition regions.
Conventional techniques for microfluidics include the use of lithographically-formed master molds (conventional positive or negative photoresist or SU-8 epoxy resin) that produce rectangular or nearly-rectangular sidewalls. Techniques have been reported that produce curvature in the sidewalls using JSR photoresist or other photoresists combined with baking processes to slump the sidewalls. These processes are not well-controlled and do not produce an inverse-circular geometry needed for replica molding. In addition, these processes do not enable smooth transitions at bifurcations or smooth changes in vessel diameter because they are essentially layer-by-layer deposition and exposure techniques, and therefore by nature they result in step changes in geometry.
Etching processes such as plasma etching or wet etching typically have the same limitations as do the lithographic techniques. Deep Reactive Ion Etching (DRIE) techniques are highly anisotropic, and, when modified to produce graded sidewalls, still produce straight walls and sharp corners. Isotropic RIE techniques and isotropic wet etching techniques typically have very slow etch rates and are not well-controlled for longer etch times and arbitrary geometries. In addition, isotropic etching does not maintain a circular aspect ratio for deeper etching processes.